Project Summary Foreign body reaction (FBR) happens to nearly all devices implanted to the body, and results in avascular fibrotic tissue deposition surrounding the implant surface, a drastic decrease of blood supply and molecular transport to the implant. FBR causes detrimental problems to the long- term functioning of current technologies to address T1D, such as subcutaneous (s.c.) insulin infusion sets, implantable glucose sensors, artificial pancreas devices by combining both glucose sensing and insulin infusion, and biomaterial-encapsulated islet transplants. Most state- of-the-art technologies have very short usage time range; For example, current infusion set needs to change and rotate its insertion site every 2-3 days to maintain healthy and vascularized infusion site, and to enhance consistent insulin absorption. Despite a strong need for overcoming FBR to fundamentally improve the longevity of device outcome, there is no effective way to do so. The long-term research goal of the PI is to develop a novel formulation as a platform technology that can be easily applied on surfaces of most existing devices to be s.c. implanted. Its major function is to resist FBR, and boost the long-term performance of its modified implanted devices. The objective of this T1D Pathfinder Award is to develop a particular type of such formulation to drastically improve the longevity of subcutaneous insulin infusion set. Two main tasks of the award involve the identification of the mechanism of failure for implanted infusion set, and identification of key formulation that prevents infusion set from stimulating FBR and retains normal insulin absorption in practical wear condition. Immunocompetent diabetic mice and rats induced by streptozotocin will be used as animal models in this study. The success of this project will directly result in an extended wear duration of commercial infusion sets and patch pumps to match the wear duration of commercial implantable glucose sensor- a technology advancement benefiting majority patients with T1D. The developed implant mate can also be applied on implanted glucose sensor to drastically increase the longevity of continuous glucose monitoring (CGM). The resulting advancement on both infusion sets and CGM in an artificial pancreas configuration will achieve a transformative impact in managing T1D. The novel topical formulation to resist FBR will also impact a broad range of implantation applications beyond T1D.